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西斯普拉丁诱导的WWP1-eccDNA表达有助于卵巢癌的耐药性

Chenyang Lu1, Li Han2,3, Xiaojuan Guo2,3

  • 1College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, China.

Advances in clinical and experimental medicine : official organ Wroclaw Medical University
|September 4, 2025
PubMed
概括

在卵巢癌 (OC) 耐药性方面,WWP1-eccDNA起着关键作用. 西斯普拉丁治疗增加了WWP1-eccDNA,从而恶化了耐药性,而氨酸则降低了耐药性,从而提供了潜在的治疗策略.

关键词:
在WWP1化学阻力滴滴数字PCR染色体外圆形DNA卵巢癌 其他

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科学领域:

  • 癌症学
  • 分子生物学
  • 遗传学

背景情况:

  • 多种药物耐药性是卵巢癌 (OC) 治疗的一个重大挑战.
  • 超染色体循环DNA (eccDNA) 涉及到瘤的开始和进展.
  • 需要进一步阐明eccDNA在瘤耐药性的具体作用,特别是OC.

研究的目的:

  • 研究WWP1-eccDNA在卵巢癌抵抗机制中的作用.
  • 评估西斯普拉丁和尿素对WWP1-eccDNA水平和瘤生长的影响.
  • 为了比较数字滴状聚合酶链反应 (ddPCR) 和实时定量聚合酶链反应 (RT-qPCR) 检测eccDNA的有效性.

主要方法:

  • 培养人类OC细胞系 (SKOV3和SKOV3/DDP) 并进行高通量测序.
  • 在裸体小鼠中使用异种移植模型,用西斯或尿素治疗.
  • 使用ddPCR和RT-qPCR量化WWP1-eccDNA,优化检测方法.

主要成果:

  • 在耐思SKOV3/ DDP细胞和瘤中,WWP1- eccDNA显著上调.
  • 西斯普拉丁治疗增加了WWP1- eccDNA水平,与耐药瘤的有限疗效相关.
  • 水氧尿素治疗减少了瘤的生长,并降低了WWP1- eccDNA水平.
  • 与RT-qPCR相比,ddPCR在检测eccDNA方面表现出更高的灵敏度.

结论:

  • WWP1-eccDNA是介导卵巢癌耐药性的关键因素.
  • 通过增加WWP1-eccDNA,西斯普拉丁会加剧耐药性,而通过降低耐药性,氨酸会显示潜在的耐药性.
  • ddPCR是癌症研究中检测和量化eccDNA的高度敏感和准确的方法.